The goal of this project is to examine the manner in which immunologic mechanisms may contribute to diseases of the nervous system. The cellular and humoral immune response to putative antigens and possible immunopathologic diseases such as multiple sclerosis (MS) are being studied. Included in these studies have been examinations of the immune response to viruses which can commonly infect the nervous system and which could be related to the induction of immunopathologic disease processes. In addition, the immune response to antigens of myelin such as myelin basic protein (MBP) and proteolipid protein (PLP) which may represent targets of immune-mediated diseases of myelin, has been studied. The T-cell response to MBP has been examined in a multiplex family with multiple affected and unaffected members in order to minimize the influence of genetic background on the response. An MBP-specific T-cell response is present in both affected and unaffected individuals. Analysis of HLA restriction and epitope specificity does not differ significantly between these family members reducing the likelihood that a unique response to MBP is responsible for disease. The T-cell response to exon II of MBP, a portion of the molecule not normally expressed in mature myelin but found in developing myelin, was also examined in a multiplex family. The greatest response was observed in the most severely affected individual in this family suggesting that the portion of MBP encoded by exon II may elicit a T-cell response which may contribute to the disease process. The importance of antigens other than those associated with the 18.5Kd form of MBP is confirmed by the identification of a T~cell response to a change isomer of MBP, C8. Using synthetic peptides, a T-cell response to PLP has also been demonstrated in both healthy controls and MS patients. Assessment of the immune response to measles virus has shown that seronegative individuals can be demonstrated in populations with a history of childhood vaccination. A good T-cell response to the virus occurs following natural infection, however, indicating that the decreased response following vaccination is not due to an inability to respond to the virus. Mechanisms of vaccine failure are being examined.